This is a 371 of PCT/IT99/00259 filed Aug. 6, 1999.
The present invention relates to pharmaceutical compositions containing N-palmitoylethanolamide (palmidrol) for use in the veterinary field, particularly for the treatment of the eosinophilic skin condition in felines which is normally known as Eosinophilic Granuloma Complex, and of tendonous keloids in horses.
The eosinophilic condition in felines (Moriello K et al, 1997, Handbook of Small Animal Dermatology, pp. 205-208, Pergamon Press) has clinical signs such as erythema, pruritis and alopecia, and skin symptoms which are recognizable in the form of eosinophilic plaque (EP), eosinophilic granuloma (EG), and miliary or papulo-scabby dermatitis, which can appear in the animal individually or simultaneously or at different times.
EP is a circumscribed area of erosion and exudation associated with clinical signs such as erythema, pruritis and auto-induced alopecia. Although they may appear anywhere on the skin surface, the lesions are located preferentially in the inguinal or perianal regions or in the medial region of the upper rear leg. The characteristic hystopathology of EP shows considerable cell infiltration in the perivascular spaces, associated with epidermal hyperplasia, spongiosis and ulceration.
EG appears as an erythematous, alopecic and raised area generally located on the caudal face of the rear paws on the extremities (the claw bed and the pads), in the oral cavity, or on the chin. The characteristic hystopathology of EG appears as a diffuse granulomatous dermatitis associated with areas of collagenolysis.
Miliary dermatitis is similar to EP but less extensive and with the formation of scabs.
Regardless of whether it is in the form of EP or EG, eosinophilic granuloma with lesions, is a highly recurrent condition. For this reason, animals suffering from eosinophilic granuloma, in the form either of EP or of EG, are subject throughout their lives, to intermittent or continuous treatments with antihistamines and corticosteroids the side effects of which, particularly in treatment of long duration, are known and documented.
The identification of active ingredients which can alleviate or resolve the inflammatory picture, at the same time ensuring maximum tolerability and an absence of adverse reactions, is an objective of considerable interest in veterinary treatment.
Tendonous keloids represent one of the most common chronic manifestations of tendinitis which arise in horsesxe2x80x94and in particular in competition horsesxe2x80x94as a result of acute inflammations of the tendons, as well as partial or complete traumatic lesions and also lesions associated with haemorrhage and oedema.
Tendonous keloids appear as soft, easily palpable masses of variable sizes and are constituted by fibrous tissue with thickenings and adhesions in the peritendonous area. Horses with chronic tendon symptoms of this type notice pain with clear lameness which greatly comprise their competitive performance.
The treatment of these symptoms, when they are chronic, is particularly complex since the anti-inflammatory drugs normally used (FANS and corticosteroids) are more effective in the acute phases than in the consequent chronic manifestations.
Up to now, various treatments have been tried with little success; in particular, it has been noted that the intratendonous administration of corticosteroids is contraindicated. Up to now, use has been made of very questionable operations such as superficial burning, percutaneous splitting of the tendons, or implantation of carbon fibres.
Basically, up to the present time, there has been no pharmacological treatment which has solved the chronic symptomatic manifestations of tendinitis in horses.
It has now surprisingly been found that N-palmitoylethanolamide (common international name palmidrol) is effective in the treatment of eosinophilic granuloma in cats, for both EP and EG lesions, and of tendonous keloids in horses. In the latter case in particular, a complete recovery of the animal with the possibility of a return to the competition circuit has been confirmed.
The subject of the present invention is therefore the use of n-palmitoylethanolamide, preferably in micronized and/or co-micronized form, for the preparation of pharmaceutical compositions for veterinary use, particularly for the treatment of eosinophilic granuloma in cats, for both EP and EG lesions, and of tendonous keloids in horses.
A further subject of the present invention is pharmaceutical compositions containing N-palmitoylethanolamide in micronized and/or co-micronized form.
The treatment of cats with N-palmitoylethanolamide provides for the administration of the drug in quantities of from 1 to 50 mg/kg/die for a period of between 15 and 60 days. A preferred treatment scheme provides for a daily administration of 10 mg/kg of body weight for 30 consecutive days.
The treatment of horses with N-palmitoylethanolamide provides for the administration of the drug in quantities of from 0.5 to 5 g/die, preferably 2 g/die for a period of between 20 and 150 consecutive days, preferably between 30 and 120 days.